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Mutations in amyloid precursor protein and presenilin-1 genes increase the basal oxidative stress in murine neuronal cells and lead to increased sensitivity to oxidative stress mediated by amyloid beta-peptide (1-42), HO and kainic acid: implications for Alzheimer's disease.
J Neurochem. 2006 Mar; 96(5):1322-35.JN

Abstract

Oxidative stress is observed in Alzheimer's disease (AD) brain, including protein oxidation and lipid peroxidation. One of the major pathological hallmarks of AD is the brain deposition of amyloid beta-peptide (Abeta). This 42-mer peptide is derived from the beta-amyloid precursor protein (APP) and is associated with oxidative stress in vitro and in vivo. Mutations in the PS-1 and APP genes, which increase production of the highly amyloidogenic amyloid beta-peptide (Abeta42), are the major causes of early onset familial AD. Several lines of evidence suggest that enhanced oxidative stress, inflammation, and apoptosis play important roles in the pathogenesis of AD. In the present study, primary neuronal cultures from knock-in mice expressing mutant human PS-1 and APP were compared with those from wild-type mice, in the presence or absence of various oxidizing agents, viz, Abeta(1-42), H2O2 and kainic acid (KA). APP/PS-1 double mutant neurons displayed a significant basal increase in oxidative stress as measured by protein oxidation, lipid peroxidation, and 3-nitrotyrosine when compared with the wild-type neurons (p < 0.0005). Elevated levels of human APP, PS-1 and Abeta(1-42) were found in APP/PS-1 cultures compared with wild-type neurons. APP/PS-1 double mutant neuron cultures exhibited increased vulnerability to oxidative stress, mitochondrial dysfunction and apoptosis induced by Abeta(1-42), H2O2 and KA compared with wild-type neuronal cultures. The results are consonant with the hypothesis that Abeta(1-42)-associated oxidative stress and increased vulnerability to oxidative stress may contribute significantly to neuronal apoptosis and death in familial early onset AD.

Authors+Show Affiliations

Department of Chemistry and Center of Membrane Sciences, University of Kentucky, Lexington, Kentucky 40506, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

16478525

Citation

Mohmmad Abdul, Hafiz, et al. "Mutations in Amyloid Precursor Protein and Presenilin-1 Genes Increase the Basal Oxidative Stress in Murine Neuronal Cells and Lead to Increased Sensitivity to Oxidative Stress Mediated By Amyloid Beta-peptide (1-42), HO and Kainic Acid: Implications for Alzheimer's Disease." Journal of Neurochemistry, vol. 96, no. 5, 2006, pp. 1322-35.
Mohmmad Abdul H, Sultana R, Keller JN, et al. Mutations in amyloid precursor protein and presenilin-1 genes increase the basal oxidative stress in murine neuronal cells and lead to increased sensitivity to oxidative stress mediated by amyloid beta-peptide (1-42), HO and kainic acid: implications for Alzheimer's disease. J Neurochem. 2006;96(5):1322-35.
Mohmmad Abdul, H., Sultana, R., Keller, J. N., St Clair, D. K., Markesbery, W. R., & Butterfield, D. A. (2006). Mutations in amyloid precursor protein and presenilin-1 genes increase the basal oxidative stress in murine neuronal cells and lead to increased sensitivity to oxidative stress mediated by amyloid beta-peptide (1-42), HO and kainic acid: implications for Alzheimer's disease. Journal of Neurochemistry, 96(5), 1322-35.
Mohmmad Abdul H, et al. Mutations in Amyloid Precursor Protein and Presenilin-1 Genes Increase the Basal Oxidative Stress in Murine Neuronal Cells and Lead to Increased Sensitivity to Oxidative Stress Mediated By Amyloid Beta-peptide (1-42), HO and Kainic Acid: Implications for Alzheimer's Disease. J Neurochem. 2006;96(5):1322-35. PubMed PMID: 16478525.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mutations in amyloid precursor protein and presenilin-1 genes increase the basal oxidative stress in murine neuronal cells and lead to increased sensitivity to oxidative stress mediated by amyloid beta-peptide (1-42), HO and kainic acid: implications for Alzheimer's disease. AU - Mohmmad Abdul,Hafiz, AU - Sultana,Rukhsana, AU - Keller,Jeffrey N, AU - St Clair,Daret K, AU - Markesbery,William R, AU - Butterfield,D Allan, PY - 2006/2/16/pubmed PY - 2006/5/12/medline PY - 2006/2/16/entrez SP - 1322 EP - 35 JF - Journal of neurochemistry JO - J. Neurochem. VL - 96 IS - 5 N2 - Oxidative stress is observed in Alzheimer's disease (AD) brain, including protein oxidation and lipid peroxidation. One of the major pathological hallmarks of AD is the brain deposition of amyloid beta-peptide (Abeta). This 42-mer peptide is derived from the beta-amyloid precursor protein (APP) and is associated with oxidative stress in vitro and in vivo. Mutations in the PS-1 and APP genes, which increase production of the highly amyloidogenic amyloid beta-peptide (Abeta42), are the major causes of early onset familial AD. Several lines of evidence suggest that enhanced oxidative stress, inflammation, and apoptosis play important roles in the pathogenesis of AD. In the present study, primary neuronal cultures from knock-in mice expressing mutant human PS-1 and APP were compared with those from wild-type mice, in the presence or absence of various oxidizing agents, viz, Abeta(1-42), H2O2 and kainic acid (KA). APP/PS-1 double mutant neurons displayed a significant basal increase in oxidative stress as measured by protein oxidation, lipid peroxidation, and 3-nitrotyrosine when compared with the wild-type neurons (p < 0.0005). Elevated levels of human APP, PS-1 and Abeta(1-42) were found in APP/PS-1 cultures compared with wild-type neurons. APP/PS-1 double mutant neuron cultures exhibited increased vulnerability to oxidative stress, mitochondrial dysfunction and apoptosis induced by Abeta(1-42), H2O2 and KA compared with wild-type neuronal cultures. The results are consonant with the hypothesis that Abeta(1-42)-associated oxidative stress and increased vulnerability to oxidative stress may contribute significantly to neuronal apoptosis and death in familial early onset AD. SN - 0022-3042 UR - https://www.unboundmedicine.com/medline/citation/16478525/Mutations_in_amyloid_precursor_protein_and_presenilin_1_genes_increase_the_basal_oxidative_stress_in_murine_neuronal_cells_and_lead_to_increased_sensitivity_to_oxidative_stress_mediated_by_amyloid_beta_peptide__1_42__HO_and_kainic_acid:_implications_for_Alzheimer's_disease_ L2 - https://doi.org/10.1111/j.1471-4159.2005.03647.x DB - PRIME DP - Unbound Medicine ER -